The long-term goal of this project is to provide new evidence for a link between taste and genetic factors that influence macronutrient selection. The overall hypothesis of this proposal is that distinct and contrasting preferences for fat or carbohydrate sources across mouse strains are genetically determined and that strain differences in taste preference(s) contribute to this macronutrient selection behavior. The primary strategies used to test this hypothesis will be studies of behavioral taste preference and macronutrient self-selection, cosegregation analysis, and genetic linkage analysis. Recently we identified a valuable model for investigating the relationship between taste and dietary selection: two novel mouse strain pairs that exhibit contrasting patterns of macronutrient selection. AKR/J and C57BL/6J mice select/consume a higher proportion of fat while the SWR/J and CAST/Ei mice select/consume a higher proportion of carbohydrate. The AKR/J vs. SWR/J model of differential macronutrient selection generalizes to many other diet paradigms however the 3-choice macronutrient selection paradigm has been identified as the most accurate and reliable behavioral phenotype to be used in the genetic analyses described in this research plan. Moreover preliminary data indicate that AKR/J and SWR/J mice also differ in their taste preferences for corn oil emulsions and for the bitter tastant sucrose octaacetate (SOA). The identification of strain differences in taste responsiveness is relevant to macronutrient selection, i.e., there is evidence for genetic control of bitter taste sensitivity, and recent studies suggest an association between bitter taste acuity and the preference for fat. Thus Specific Aim 1 will examine the taste preference responses to corn oil and SOA in the second novel strain pair (C57BL/6J and CAST/Ei), using two-bottle preference tests. In Specific Aim 2, a genetic analysis of the mode of inheritance of the behavioral phenotypes will be performed using an F2 intercross breeding strategy (AKR/J x SWR/J and C57BL/6J x CAST/Ei). The availability of two strain pairs with contrasting patterns of macronutrient selection and taste preferences will also permit a cosegregation analysis in the F2 progeny to determine whether there is evidence for a common genetic mechanism underlying differences in fat or carbohydrate preference and bitter taste sensitivity. However the most important potential result of this research plan is the ability to locate the chromosomal positions of genes underlying the macronutrient selection behavior. Thus in Specific Aim 3, a genetic mapping study will be carried out using the quantitative trait loci (QTL) strategy of performing a whole genome screen in two F2 populations. The results of these studies will provide a new understanding of the taste and genetic mechanisms underlying macronutrient selection.